Search

Total synthesis of (±)-sesbanine ( 1 ) was carried out using γ-addition of ketene silyl acetal of methyl 3-cyclopentenecarboxylate to quaternized methyl nicotinate. The resulting 1,4-dihydropyridine ( 7 ) was oxidized with DDQ to give 4-substituted nicotinate ( 2 ) and 2 was converted to alcohol ( 8 ) by stereoselective oxymercuration followed by treatment with ammonia to give 1 .

Reactions of 3-substituted 2-nitrosoimino-2,3-dihydrobenzothiazoles (1) with phenyl- and n-butyllithiums give the corresponding (N-substituted o-amino)phenyl sulfides as the major product due to direct attack on the sulfur atom of the benzothiazoline ring, while that with benzyllithium gives 2,2-dibenzyl derivatives and bis[o-(N-substituted amino)phenyl] disulfides. The difference between the reactions of 1 with Grignard reagents and those with organolithiums has been explained by the difference of the coordination site, thiophilicity and the ionic character of the reagents.

Debromination of 4-aryl- or 4-alkenyl-3-bromo-4,6-dimethyl-3,4-dihydro-2-pyrone ( 1 ) with AgSbF6 in dichloromethane or 1,2-dichloroethaneinduced rearrangement of the aryl or alkenyl group to the 3-position to afford the corresponding 3-substituted 2-pyrone ( 6 ) in high yield.

An efficient method is described for the synthesis of ethyl 1-(2-oxoalkyl)-1,2-dihydroisoquinoline-2-carboxylates by C–C bond formation between 2-ethoxycarbonylisoquinolinium chloride and trimethylsilyl enol ethers. The products were treated with a few bases to afford the corresponding pyrido [2,1-a] isoquinoline derivatives.

The reaction of 3-aryl-5-benzoyl-2-imino-2,3-dihydro-1,3,4-thiadiazoles (6) with dimethyl acetylenedicarboxylate (4b) gave the corresponding thiazole (8) and benzoyl cyanide through sulfurane (B) by 1,3-dipolar cycloaddition and cis- (9) and trans-vinyl (10) compounds through zwitterion (C) by simple addition. Two types of addition reactions competed each other and the ratio of the two [R=B/C] depended solely on the solvent polarity (ET). Dibenzoylacetylene behaved similarly. Several iminothiazolines and iminothiadiazolines reacted with activated acetylenes and the selectivity for the two types of addition reactions for each system was shown to be affected by quite subtle balance of electron-withdrawing ability of each heterocycle.

3-Substituted 2-nitrosoimino-2,3-dihydrobenzothiazoles (1) react with benzylmagnesium chloride to give 3-substituted 2,2-dibenzyl- (2), 2-N′-benzylidenehydrazono- (3) and 2-N′,N′-dibenzylhydrazono-2,3-dihydrobenzothiazoles (4). The main reaction (formation of 3 and 4) occurrs on the nitroso group of 1, which proceeds via 1,2-addition intermediate (B). Allylmagnesium bromide and cinnamylmagnesium chloride also react with 3-methyl derivative (1a) to afford 2-N′,N′-diallyl- and 2-N′-(1-phenyl-2-propenyl)hydrazono-3-methyl-2,3-dihydrobenzothiazoles, respectively.

Hypervalentスルフランに関する3種の典型的な反応と性質に関して著者らの研究を中心にまとめている。第一に,イミノチアゾリン類は遮蔽された(masked)1,3-双極子として活性アセチレンおよびイミド酸エステル類,ニトリル類と反応し,チアチオフテン型スルフラン(10-S-3)を中間体としてそれぞれ付加一脱離あるいは付加一環変換反応を行なう。第二に,中間体のスルフラン(10-S-3)が対称形になるような系を設計すると5-(2-アミノビニル)イソチアゾール系では中性鮒下で,5-(アミンメチレンアミノ)-1,2,4-チアジナゾール系で酸性条件下で可逆的環変換(結合交換)を行なうことを見いだした。それらの速度論的研究の例は以下のとおりである;前者([28d]では:〓=6.21×10-6s-1,ΔH=12.2kcal/mol,ΔS=-41e.u.;後者(〔26-H+〕)では:〓=-104.5-10+.4s-1。第三に,ジベンゾチラゾシニウム系においては,家ルポニオ基とアミノ基め1,5-渡環相互作用により新規スルフラン(10-S-4)が生成することを学結晶のX線回折により証明した。スルフラン上の置換基の電子求引性が増大するにっれて,N-S結合距離は減少し,硫黄原子の立体配置はよりよくTBP配置に近づくと同時に,その電子的効果が結合を介してアミノ基上に伝達されることが1H-NMRの化学シフトにより明らかにされた。

Allylsilanes ( 2 ) reacted with α-chlorosulfides ( 1 ) containing a carbonyl group either at α, β, or γ position to substitute exclusively for the chlorine atom of 1 and the corresponding α-allylsulfides ( 3 ) were obtained in high yields.

Dialkyl 2-(o-acylbenzoyl)-1,2-dihydro-1-isoquinolyl-phosphonates (1) were prepared by reactions of isoquinoline, o-acylbenzoyl chloride, and trialkyl phosphites. Treatment of 1 with lithium diisopr...

Substituents at 5-position of 5-amino-3-methyl- and 3-p-chlorophenyl-5-methylisothiazoles (7 and 8) were silylated and then lithiated to couple with aromatic nitriles in order to afford the adducts (4 and 5) via 1,3-silyl group shift. Desilylation of 5 with TBAF gave solely non-ring-transformed product (3-α-form). By using the pure sample of 3-α-form, the reversible ring-trans- formation (bond switch) was observed under neutral conditions for the first time.

Heteroaromatic cations such as 9-heteroniaanthracene (acridinium, xanthylium, and thioxanthylium) and 1-thionianaphthalene (thiochromenylium) ions reacted with trimethyl phosphite in the presence of sodium iodide in acetonitrile at room temperature to give the corresponding phosphonates (2 and 4) respectively in 76–92% yields. The phosphonates were deprotonated with butyllithium in THF at −78 °C, and the resulting carbanions reacted with p-tolualdehyde, cinnamaldehyde, and 4,4′-dichlorobenzophenone to afford the corresponding exomethylene containing heterocyclic compounds, respectively, in 52–96% yields. However, the phosphonate carbanions derived from 2 did not react with cycloalkanones and butanal.

The adducts (3) of triethylphosphine (1) and several isothiocyanates (2) were prepared. Equilibrium constants of the adducts (5) from tributylphosphine (4) and phenyl (2b), benzoyl (2e), and p-toluenesulfonyl isothiocyanates (2f) were determined in some solvents. The 31P chemical shifts of 5 were measured in DMF, and correlated with Hammett σp constants. Reactions of 3e with 1 and 2e gave phosphonium thiocyanates of 6 and 7, and of 11, respectively. Methylation of 3e gave S-methyl N-benzoylmonothiocarbamate (16).

Lewis acid (SnCl4) catalyzed reaction of ethyl α-chloro-α-( p -chlorophenylthio)acetate ( 1b ) with several olefins afforded the corresponding γ-butyrolactones ( 9 ) in good yields (51 – 92%). Under almost the same conditions, α-( t -butylthio)-α-chloroacetone ( 1c ) reacted with olefins to give the expected 4,5-dihydrofurans ( 10 ) in moderate yields (41 – 55%).

A series of 12-substituted 6-methyl-5,6,7,12-tetrahydro-12-X-dibenz[c,f][1,5]azastibocine (1) and azabismocine (2) were prepared. Both 1 H and 13 C NMR signals of the N-methyl group were shifted to downfield by electron-withdrawing substituent at the pnictogen atoms and the shift was linearly correlated with Hammett σ m values.

Ethyl α-chloro-α-phenylthioacetate reacted with 1-alkenes in CH2Cl2 at -78–0°C in the presence of SnCl4 to afford the ene reaction products (80–90%), which were readily converted into the corresponding γ-butyrolactones.

The existence of ring transformation equilibrium (bond switch) in 5-(1-aminoethylideneamino)-3-methyl-1,2,4-thiadiazole (5a) was confirmed by nitrogen-15 labeling experiment. Kinetic studies were carried out under neutral or acidic conditions. Kinetic parameters of the intramolecular equilibration of the monoprotonated 5a (5a-H+) were obtained by line shape analyses of the 1H NMR, i.e., ΔG273\eweq=14.8±0.2, ΔH\eweq=11.6±1.0 kcal·mol−1 ΔS\eweq=−12±3 eu, k273=9 s−1. Position of protonation was determined at the nitrogen of the ethylideneamino part of the amidino group. It was concluded that the central sulfur atom moves back and forth in the range of 0.38 A nine times a second at 0 °C, that is, bond switching.

Tributylstibine is an efficient reagent for debromination of phenacyl and arylmethyl bromides. The mechanistic difference between stibine and phosphine is discussed briefly.

In the presence of a catalytic amount of bismuth trichloride (5 mol%), silyl enol ethers react with aldehydes at room temperature to give the corresponding aldols in good yields.

RCu · BF 3 , generated in situ from Grignard reagents, CuI, and BF 3 · OEt 2 , added to aldimines containing α-hydrogens to afford secondary amines in good yields. Boron trifluoride complex of dialkylcuprate gave essentially the same result with wider application.

2-Siloxy-4H-pyrans ( 3 ) were prepared from 2-siloxypyrylium salt ( 2 ) by the addition of organocuprates to 4-position with good regioselectivity. The product 3 reacted with some electrophiles to give the corresponding 3,4-disubstituted 3,4-dihydro-2-pyrones ( 6 – 8 ).

Regiospecific synthesis of 4-substituted pyridines is attained via alkylation of diisopropyl 1-ethoxycarbonyl-1, 4-dihydropyridine-4-phosphonate followed by treatment with butyllithium. The phosphonate is prepared directly from pyridine in one pot.

An efficient method to synthesize 1-β-keto substituted 2-ethoxycarbonyl (or 2-acetyl)-1,2-dihydroisoquinolines ( 3 ) is described, utilizing boron enolates and isoquinolinium salts. The products were treated with sodium ethoxide to afford the corresponding cyclic compounds ( 6 ).

A remarkably stable hexacoordinate bismuth ate complex (1A) with two bidentate ligands was synthesized by the reaction of a pentacoordinate bismuth compound bearing a Bi-Cl bond (7) with a dilithiated reagent (2). The complex was stable up to 150 °C and was decomposed by water to afford an alcohol (11) quantitatively.

3-Substituted 2-nitrosoimino-2,3-dihydrobenzothiazoles (1) were reduced with lithium aluminum hydride to give the corresponding thiazolone azines and bis[o-(N-substituted N-formylamino)phenyl] disulfides as major products. Reactions of 1 with some substituted diazomethanes gave the corresponding unsymmetrical azine N-monoxides (16) or azines (17) depending on the structure of the diazomethane.

The reaction of 3-substituted 2-nitrosoimino-2,3-dihydrobenzothiazoles (1) with Grignard-type reagents of 3-substituted 2-imino-2,3-dihydrobenzothiazoles (2) gave azamonomethinecyanines (3) in high yields (71–96%). This is a new type of reaction for the preparation of 3. Hydrolysis of 3 afforded ring-opened disulfides, bis[o-{N-methyl-N-(3-methyl-2,3-dihydrobenzothiazol-2-ylidenecarbamoyl)amino}-phenyl] disulfides, in high yields (78–85%). Formation of by-products is explained by the presence of transnitrosation between 1 and 2 and ring-opening equilibrium of Grignard-type reagent of 2-imino-3-phenyl-2,3-dihydrobenzothiazole.

N,N-Dimethyl-2-(alkylthio)ethylamines and 3-methylthiazolidines underwent N-methylation both with trimethyloxonium tetrafluoroborate (3a) and with methyl iodide. In the methylation of N,N-dimethyl-o-(methylthio)aniline, the main reaction was S-methylation. On the other hand, in the o-ethylthio derivative, S-methylated product was major with methyl iodide, while N-methylated product was major with 3a. In the N-ethyl or N-benzyl derivative, only S-methylation occurred with both reagents. 3-Methyl-2, 2-diphenyl-2,3-dihydro-benzothiazole gave S-methylated product with 3a, suggesting that S-methylation becomes major when the 2-substituent is bulkier. 4-Methyl-3,4-dmydro-2H-benzo[b][1,4]thiazine was methylated on the nitrogen with 3a, while it gave S-methylated product with methyl iodide. Phenothiazines and 1-dialkylamino-8-(methylthio)naphthalenes gave only S-methylated products. The selective S-methylation in the case of N-methylation was carried out through protonation on the nitrogen atom followed by methyl...

Synthese des nicotinates du titre substitues en 1 par R (R=alcoxycarbonyl, acetyl ou dimethylcarbamoyl) par action d'enol ethers de silicium sur des chlorures de R-1 methoxycarbonyl-3 pyridiniums; leur addition de Diels Alder conduit (apres desulfonylation) aux R-1 dichloro-6,8 dihydro-1,4 oxo-2' alkyl-4 quinoleinecarboxylates-3. Stereochimie

5-Amino-3-methyl- and 5-amino-3-phenylisothiazoles (3a and 3b) afforded 1 : 1 adducts with aromatic nitriles and imidates. On the basis of their spectral data and the structure of hydrolysis products, the adducts were identified as 3-substituted 5-(2-aminovinyl)-1,2,4-thiadiazole derivatives (2a-g), where ring transformation took place from isothiazole to 1,2,4-thiadiazole.

The rate of methyl transfer to pyridine-d5 of δ-ammoniomethylsulfurane, i.e., S,N-dimethyl-6,7-dihydro-5H-dibenzo [b,g][1,5] thiazocinium salt ( 1 ), was slower by 1300 times than that of methyldiphenylsulfonium salt ( 3 ). Activation parameters at 25 °C were obtained for 1 ,ΔH≠=23.1,ΔS≠=−7.8, and for 3 ,ΔH≠=18.1 kcal/mol,ΔS≠=−10.3 e.u., which are in accord with the hypervalent bonding of 1 .

A stable pentacoordinate bismuth compound ( 1 ) with a five-membered ring was synthesized. Reaction of 1 with sulfuryl chloride afforded a novel stable compound ( 4 ) with a covalent BiCl bond. The compound was useful for the synthesis of other hypervalent bismuth compounds with different BiC bonds such as 1c , and the selectivity in the chlorination of 1c was described.

Reactions of 3-methyl-2,3-dihydrobenzothiazole-2-thione (1) and 3-methyl-2-(methylthio)benzothiazoliumiodide with Grignard reagents gave 2,2-disubstituted 3-methyl-2,3-dihydrobenzothiazole (2) as a major product as well as 2,2′-disubstituted 3,3′-dimethyl-2,2′,3,3′-tetrahydrobi(2-benzothiazolyl) (3). Reactions of 1 with organolithiums gave 2 as a major product. The results demonstrate that the formation of 3 is due to the presence of transition metals as an impurity in magnesium.

トリフェニルアンチモンジブロミド[2a]によりα-ケトアルコール類を酸化した。こめ酸化反応は,まず最初塩基によりアピカル位の配位子(臭素)がアルコキシル基に交換しhypervalentアンチモン化合物[D]またはスチボニウム塩[E]が生じ,つぎにα-カルビニル水素が引き抜かれてトリフェニルスチビンが生じるとともにα-ジゲトンが生成する経路(1)と五員環中間体[F]を経由して酸化する経路(2)が考えられる。一方,アピカル位の基を2-ピリジニルオキシ基で置換した五価アンチモン化合物[2d]を合成した。この化合物を用いると塩基を加えることなしに非常にすみやかにかつ収率よくα-ケトアルコールをα-ジケトンに酸化できた。トリフェニルスチビン[1a]の脱臭素反応と[2a]の酸化能を組み合わせることにより,触媒量のアンチモン化合物[1a]または[2a]でα-ケトアルコールをα-ジケトンに酸化できることを見いだした。

3-Substituted 2-nitrosoimino-2,3-dihydrobenzothiazoles (1) react with arylmagnesium bromide to give 3-substituted 2,2-diaryl-2,3-dihydrobenzothiazoles as the major product and 2-N′-arylhydrazono-2,3-dihydrobenzothiazoles as a minor product. 1 reacts also with t-butylmagnesium chloride to give 3-substituted 2-t-butyl- and 2-N′-t-butylhydrazono-2,3-dihydrobenzothiazoles and 2,3-dihydrobenzothiazol-2-one. Reaction of 1 with mesitylmagnesium bromide gave a similar result to that with t-butylmagnesium chloride.

t-butyldimethylsilyl enol ethers containing an amino group were obtained in good yields (70–90%) by the reaction of t-butyldimethylsilyl enol ethers with dimethyl(methylene)ammonium iodide (the Eschenmoser salt).

RCu·BF3 reacted with 1-ethoxycarbonylpyridinium chloride at the 4-position with almost complete regio-selectivity (>99%) to afford the corresponding 1,4-dihydropyridine derivatives in high yields (81–94%). The dihydropyridines were oxidized by oxygen to give 4-alkyl(aryl)pyridines (38–68%). Grignard reagents also reacted with 1-t-butyldimethylsilylpyridinium triflate with almost complete regioselectivity (>99%) to afford the corresponding 1,4-dihydropyridines, which were easily oxidized by oxygen to give 4-substituted pyridines in higher yields than above (58–70%).

The structure of the 1:1 adduct of “Hector’s base” with arylcyanamides was determined by X-ray analysis of tris-p-bromophenyl derivative (1a). The molecule is almost planar and the strong interaction was exemplified between the sulfur and the nitrogen atoms.

Equilibrium constants of the adduct (3c) from tributylphosphine (4) and phenyl isothiocyanate (5c) were measured in some solvents and 31P-NMR chemical shifts of the adducts (3) from (4) and isothiocyanates (RNCS) (5) were measure in DMF and correlated linearly with the σp values of the R groups.

In the presence of bismuth(III) chloride—metallic zinc or bismuth(III) chloride—metallic iron, allylic halides were found to react with aldehydes under mild conditions to give the corresponding homoallylic alcohols in high yields with high chemoselectivity.

Lithium ester enolates react with enolizable aldimines in the presence of dimethylaluminium chloride to afford β-lactams ingood yields.

Trimethylsilyl enol ethers ( 1 ) reacted with 1-ethoxycarbonylpyridinium chloride ( 3 ) at 4-position with high regioselectivity to afford 1-ethoxycarbonyl-4-(2-oxoalkyl)-1,4-dihydropyridines ( 4 in 42 – 87% yields. When 2, 2, 2-trichloroethyl chloroformate was employed, yields of the corresponding 1,4-dihydropyridines ( 8 0 were higher (80 – 100% yields). 4 and 8 were oxidized by oxygen or AgNO3 to give 4-(2-oxoalkyl)pyridines ( 12 : 30 –65%).